Ex Vivo Preservation in Vascularized Composite Allotransplantation: State of the Art, Challenges, and Perspectives

Vascularized composite allotransplantation (VCA) offers unparalleled reconstructive possibilities in complex cases but remains constrained by high immunogenicity and marked susceptibility to ischemia-reperfusion injury (IRI), particularly in muscle-rich grafts. Static cold storage (SCS), the current clinical standard, preserves grafts only for short durations. In contrast, machine perfusion (MP), already transformative in solid organ transplantation, is emerging as a promising strategy for VCA. This review summarizes the main challenges of ex vivo VCA preservation and current perfusion strategies designed to overcome them. Particular attention is given to physiological and technical factors influencing graft integrity, as well as innovations in perfusate composition and protective additives that mitigate IRI and support tissue preservation. Beyond simple storage, MP platforms enable functional assessment and therapeutic interventions, including graft reconditioning and immune modulation prior to transplantation. Complementary subzero static preservation methods, such as supercooling and cryopreservation, also show promise for substantially extending preservation times. Together with advances in experimental models, these approaches are reshaping the preservation landscape. As the field evolves, MP is poised to become a cornerstone technology in VCA, improving graft quality, extending preservation duration, and enabling pre-implantation modification strategies to reduce rejection and enhance long-term outcomes.